Jiang Hu-Lin, Kwon Jung-Taek, Kim Eun-Mi, Kim You-Kyoung, Arote Rohidas, Jere Dhananjay, Jeong Hwan-Jeong, Jang Mi-Kyeong, Nah Jae-Woon, Xu Cheng-Xiong, Park In-Kyu, Cho Myung-Haing, Cho Chong-Su
Department of Agricultural Biotechnology, Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-921, South Korea.
J Control Release. 2008 Oct 21;131(2):150-7. doi: 10.1016/j.jconrel.2008.07.029. Epub 2008 Jul 26.
Chitosan and chitosan derivatives have been proposed as alternative and biocompatible cationic polymers for non-viral gene delivery. However, the low transfection efficiency and low specificity of chitosan is an aspect of this approach that must be addressed prior to any clinical applications. In the present study a chitosan derivative, galactosylated poly(ethylene glycol)-chitosan-graft-polyethylenimine (Gal-PEG-CHI-g-PEI), was investigated as a potential hepatocyte-targeting gene carrier. The composition of Gal-PEG-CHI-g-PEI was characterized using (1)H nuclear magnetic resonance ((1)H NMR), and the particle size and zeta potential of Gal-PEG-CHI-g-PEI/DNA complexes were measured using dynamic light scattering (DLS). The Gal-PEG-CHI-g-PEI exhibited lower cytotoxicity compared to PEI 25K as a control. Likewise, Gal-PEG-CHI-g-PEI/DNA complexes showed good hepatocyte specificity. Furthermore, Gal-PEG-CHI-g-PEI/DNA complexes transfected liver cells more effectively than PEI 25K in vivo after intravenous (i.v.) administration. Together, these results suggest that Gal-PEG-CHI-g-PEI, which has improved transfection efficiency and hepatocyte specificity both in vitro and in vivo, may be useful for gene therapy.
壳聚糖及其衍生物已被提议作为用于非病毒基因递送的替代性生物相容性阳离子聚合物。然而，壳聚糖的低转染效率和低特异性是该方法在任何临床应用之前必须解决的一个方面。在本研究中，研究了一种壳聚糖衍生物，半乳糖基化聚（乙二醇）-壳聚糖-接枝-聚乙烯亚胺（Gal-PEG-CHI-g-PEI）作为一种潜在的肝细胞靶向基因载体。使用氢核磁共振（¹H NMR）对Gal-PEG-CHI-g-PEI的组成进行了表征，并使用动态光散射（DLS）测量了Gal-PEG-CHI-g-PEI/DNA复合物的粒径和zeta电位。与作为对照的PEI 25K相比，Gal-PEG-CHI-g-PEI表现出更低的细胞毒性。同样，Gal-PEG-CHI-g-PEI/DNA复合物显示出良好的肝细胞特异性。此外，静脉内（i.v.）给药后，Gal-PEG-CHI-g-PEI/DNA复合物在体内转染肝细胞的效率比PEI 25K更高。总之，这些结果表明，Gal-PEG-CHI-g-PEI在体外和体内均具有提高的转染效率和肝细胞特异性，可能对基因治疗有用。
